BMJ 2013;346:f2028 doi: 10.1136/bmj.
f2028 (Published 16 April 2013)
Clinical Review
Pulmonary hypertension: diagnosis and management
1 1
David G Kiely consultant respiratory physician , Charlie A Elliot consultant respiratory physician ,
12
Ian Sabroe consultant respiratory physician , Robin Condliffe consultant respiratory physician
National Pulmonary Hypertension Service (Sheffield), Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals
1
NHS Foundation Trust, Sheffield S10 2JF, UK; 2Academic Unit of Respiratory Medicine, Department of Infection and Immunity, Faculty of Medicine,
Dentistry and Health, Medical School, University of Sheffield, Sheffield, UK
Pulmonary hypertension was previously considered a rare
untreatable condition. The past two decades have seen major
changes in our understanding of the spectrum of disease
affecting the pulmonary circulation. More than 30 randomised
controlled trials (RCTs) of treatments have been performed,
and surgery for patients with chronic thromboembolic
pulmonary hypertension has been developed. Advances in
imaging have enabled more detailed patient assessment, but
pulmonary hypertension continues to be a life shortening
condition, and there is often a delay of around two years from
onset of symptoms to diagnosis.1 This article focuses on adult
pulmonary hypertension in primary and secondary care, its
diagnosis, and management.
What is pulmonary hypertension and how
common is it?
Pulmonary hypertension is defined at cardiac catheterisation as
a mean pulmonary artery pressure of 25 mm Hg or more. The
initial clinical classification in 1973 arose from a World Health
Organization sponsored international meeting after an epidemic
related to use of the appetite suppressant, aminorex fumarate.2
It defined primary pulmonary hypertension (now termed
idiopathic pulmonary arterial hypertension) as being
characterised by vasculopathy of the pulmonary arteries. Better
understanding of disease mechanisms led to subsequent
classification of conditions with shared clinical and
pathophysiological characteristics:
Group 1: Pulmonary arterial hypertension (PAH), which can
be idiopathic (IPAH) or associated with other conditions,
notably systemic sclerosis and congenital heart disease
Group 2: Pulmonary hypertension owing to left heart disease
(PH-LHD)
Group 3: Pulmonary hypertension owing to lung disease or
hypoxia (PH-Lung), or both
Group 4: Chronic thromboembolic pulmonary hypertension
(CTEPH)
Group 5: Unclear or multifactorial mechanisms (fig 1⇓).3
Correspondence to: D G Kiely david.kiely@sth.nhs.uk
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CLINICAL REVIEW
1
Many mechanisms can lead to elevation of pulmonary pressures.
In PAH, progressive narrowing of the pulmonary arterial bed
results from an imbalance of vasoactive mediators, including
prostacyclin, nitric oxide, and endothelin-1. This leads to an
increased right ventricular afterload, right heart failure, and
premature death. Between 11% and 40% of patients with IPAH
and 70% of patients with a family history of PAH carry a
mutation in the gene encoding bone morphogenetic receptor-2
(BMPR2); however, penetrance is low—carriers have a 20%
lifetime risk of developing pulmonary hypertension.4 5 Therefore,
“multiple hits” are probably needed for the development of
PAH. In PH-LHD, raised left atrial pressures result in secondary
elevation of pulmonary pressure. In PH-Lung, raised pulmonary
arterial pressures result from mechanisms such as vascular
destruction and hypoxic vasoconstriction. In CTEPH,
mechanical obstruction of the pulmonary vascular bed is the
primary process.
Incidences are estimated to be 1-3.3 per million per year for
IPAH and 1.75-3.7 per million per year for CTEPH; the
prevalence of PAH is estimated at 15-52 per million.6-10
Pulmonary hypertension is more common in severe respiratory
and cardiac disease, occurring in 18-50% of patients assessed
for transplantation or lung volume reduction surgery, and in
7-83% of those with diastolic heart failure.11-14
Who gets pulmonary hypertension and
why is classification important?
IPAH is rare and primary care doctors may never encounter a
case. By contrast, the prevalence of PAH is high in certain
patient groups, such as those with systemic sclerosis (9%), portal
hypertension (2-6%), congenital heart disease (5-10%), and
HIV (0.5%).15-20 Between 0.5% and 4% of patients develop
CTEPH after acute pulmonary embolism; patients at increased
risk include those presenting with large, recurrent, or
unprovoked clots.21 22 Classification is crucial in determining
treatment and prognosis.9 Specific treatments exist for PAH and
CTEPH. By contrast, in PH-LHD and PH-Lung, treatment is
best directed at the underlying condition, and currently PAH
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BMJ 2013;346:f2028 doi: 10.1136/bmj.f2028 (Published 16 April 2013) Page 2 of 12

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Summary points
Pulmonary hypertension has many causes so prognoses and treatments vary
The condition is diagnosed by systematically evaluating the breathless patient and screening patients at high risk
Patients at high risk of severe and treatable pulmonary hypertension include those with systemic sclerosis, portal hypertension, congenital
heart disease, and previous pulmonary embolism
Specialist centres provide access to tailored investigative and treatment pathways and support networks for patients
Patients with severe pulmonary hypertension can deteriorate rapidly—do not delay referral to perform specialist investigations
Only selected patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension benefit from interventions
directed at pulmonary vasculature; for most patients treatment is aimed at the underlying condition

Sources and selection criteria

This review is based on our personal experience, personal archives of references, and a PubMed search using terms including pulmonary
hypertension, chronic thromboembolic disease, and prognosis. We consulted international guidelines from the European Society of Cardiology,
European Respiratory Society, and American College of Chest Physicians.

specific treatments are not recommended. Distinguishing
between IPAH and PH-LHD due to diastolic dysfunction in the
setting of normal left ventricular systolic function may be
challenging (table 1⇓).
Median survival in untreated IPAH is 2.8 years, but more recent
registries have observed overall median survival of at least five
years.9 23 In the past, the mean age at diagnosis in IPAH was 35
years; current five year survival in this younger age group is
now about 75%.10 PAH associated with systemic sclerosis carries
a worse prognosis than IPAH, whereas the opposite is true for
congenital heart disease.9 The development of pulmonary
hypertension in cardiac and respiratory disease has a negative
impact on prognosis, which depends on the underlying cause
and severity of pulmonary hypertension.
What are the symptoms and signs of
pulmonary hypertension?
PAH most commonly presents with progressive breathlessness.24
As right ventricular dysfunction develops patients can
experience exertional dizziness and syncope. Oedema and ascites
occur late in the disease. Anginal chest pain may occur due to
exertional myocardial hypoperfusion in the setting of right
ventricular hypertrophy, left main coronary artery compression
by the pulmonary artery, or ischaemic heart disease.25 Patients
are prone to tachyarrythmias, most commonly atrial flutter,
which can cause sudden decompensation.26 Haemoptysis,
although uncommon, can occur in Eisenmenger’s syndrome
and CTEPH, where bronchial arteries may be enlarged. Signs
suggestive of pulmonary hypertension include a loud pulmonary
second heart sound, systolic murmur of tricuspid regurgitation,
raised jugular venous pressure, peripheral oedema and ascites,
but these signs may be subtle or absent in early disease. Look
for signs of associated conditions (such as connective tissue
disease or liver disease).
When should I suspect pulmonary
hypertension?
Pulmonary hypertension is diagnosed by systematically
evaluating the breathless patient and screening high risk groups.
Unexplained progressive exertional breathlessness in the absence
of symptoms or signs of respiratory or left heart disease is
suggestive. Screening protocols exist for high risk groups.
Rheumatology centres screen patients with systemic sclerosis
annually, and potential liver transplant recipients are routinely
investigated for portopulmonary hypertension. Persistent
breathlessness after pulmonary embolism should alert the doctor
to the possibility of CTEPH.
What investigations should I perform if
pulmonary hypertension is suspected?
Electrocardiography, chest radiography, and pulmonary function
tests may identify an alternative cause of breathlessness (fig
2⇓). Evidence of right heart strain on electrocardiography and
prominent pulmonary arteries or cardiomegaly on chest
radiography were seen in 80-90% of cases in a large IPAH
registry.24 In clinical practice, however, a normal
electrocardiograph and chest radiograph cannot exclude the
diagnosis. A reduction in gas transfer (lung capacity to “transfer”
an inhaled gas into the blood) and mildly deranged spirometry
both occur in IPAH.27 If pulmonary hypertension is still
suspected, echocardiography should be performed.28 Figure 3⇓
describes the estimation and interpretation of systolic pulmonary
artery pressure, together with other echocardiographic features
suggesting the presence of pulmonary hypertension. Importantly,
pulmonary hypertension is defined by mean pulmonary artery
pressure (measured at right heart catheterisation) not systolic
pulmonary artery pressure (estimated by echocardiography). In
addition, systolic estimates are less accurate in respiratory
disease and during intercurrent illness.14
How is pulmonary hypertension assessed
in a specialist unit?
If initial investigations suggest that pulmonary hypertension is
possible, further tests are needed to confirm the diagnosis and
to establish cause and severity. In the United Kingdom, a
network of specialist centres was commissioned in 2001 to
standardise and improve care (box 1). If severe disease is
suspected, do not delay referral to a specialist centre, although
imaging to exclude thromboembolic disease may be considered.
If the degree of pulmonary hypertension seems to be
disproportionate to the underlying cardiorespiratory disease, or
if diagnostic doubt exists, discussion with a specialist centre is
recommended. In these groups it is also important to exclude
coexisting thromboembolic disease as a cause of pulmonary
hypertension. Accurate classification and assessment of disease
severity (fig 2) requires integration of clinical, physiological,
and radiological data. This is central to further management (fig
4⇓).

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BMJ 2013;346:f2028 doi: 10.1136/bmj.f2028 (Published 16 April 2013)
Box 1 UK designated pulmonary hypertension centres for adults and children
Nationwide
UK national centres: www.pulmonaryhypertensioncentres.co.uk
Glasgow
Golden Jubilee Hospital: www.spvu.co.uk
Newcastle
Freeman Hospital: www.newcastle-hospitals.org.uk
Sheffield
Royal Hallamshire Hospital: www.thoracic.group.shef.ac.uk
Cambridge
Papworth Hospital: www.papworthhospital.nhs.uk
London
Royal Brompton Hospital: www.rbht.nhs.uk
Hammersmith Hospital: www.pulmonary-hypertension.org.uk
Royal Free Hospital: www.royalfree.nhs.uk
Great Ormond Street (children): www.gosh.nhs.uk
Blood, exercise testing, and overnight
oximetry
Immunological and HIV testing may identify a cause of
pulmonary hypertension. Brain natriuretic peptide (BNP) and
N-terminal-pro-BNP have prognostic importance. Lower levels
at baseline and improvement during follow-up are associated
with better outcomes.29 30 The six minute walk test has been
extensively evaluated. It provides functional and prognostic
information and can be used to monitor treatment response.31 32
Cardiopulmonary exercise testing in selected patients gives
more detailed physiological and prognostic information.33
Overnight oximetry is performed if sleep disordered breathing
is a suspected cause.
Imaging
Isotope perfusion lung scanning has high sensitivity for CTEPH
and a normal scan excludes the diagnosis, whereas increased
renal isotope uptake may identify right to left shunts and explain
hypoxaemia.34 35 High resolution computed tomography and
computed tomography pulmonary angiography visualise the
pulmonary arterial tree and provide a wealth of additional
diagnostic information (fig 5⇓). Direct features of chronic
thromboembolic disease include occlusions, stenoses, and
intraluminal webs (fig 1), whereas indirect signs include a
mosaic perfusion pattern. These signs can be subtle and may be
missed by a non-specialist radiologist. Magnetic resonance
imaging provides a radiation-free method of quantitatively
assessing cardiac structure and function, prognosis, and response
to treatment.36 37 Magnetic resonance pulmonary angiography
can supplement computed tomography pulmonary angiography
in the assessment of CTEPH operability, and magnetic resonance
perfusion imaging is as sensitive as isotope perfusion lung
scanning.38 39 Pulmonary angiography is not commonly used in
the UK to select CTEPH patients for pulmonary endarterectomy,
but is used widely in other centres throughout the world to assess
for surgical accessibility.
Right heart catheterisation
If non-invasive investigations support a diagnosis of pulmonary
hypertension, right heart catheterisation is needed to confirm
the diagnosis by directly measuring pulmonary pressure. It also
allows measurement of cardiac output and estimation of left
atrial pressure using pulmonary arterial wedge pressure.
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Haemodynamic parameters (such as right atrial pressure, cardiac
index, and pulmonary vascular resistance) and pulmonary artery
saturations have important prognostic value. Raised pulmonary
arterial wedge pressure is suggestive of PH-LHD. Changes in
oxygen saturations between right sided cardiac chambers may
suggest an intracardiac shunt. Vasoreactivity testing, usually
using inhaled nitric oxide, can identify patients with IPAH who
may respond to long term high dose calcium channel blockers.
A positive response is defined as a reduction in mean pulmonary
artery pressure of at least 10 mm Hg, to less than 40 mm Hg,
without a fall in cardiac output.40
What treatments are available for
pulmonary hypertension?
Supportive treatment
Patients with CTEPH require anticoagulants because of the
central role of thromboembolic disease. Although
anticoagulation is recommended in IPAH, its role in PAH
associated with other conditions is less clear.41 42 Diuretics are
often needed to treat heart failure. Digoxin and long term oxygen
therapy may be considered, but there is no evidence from RCTs
on their use. Annual flu vaccination is recommended.43
Pregnancy is poorly tolerated despite changing practices,44 and
a recent systematic review found that maternal mortality remains
high (17-33%).45 Women are counselled about the high risks
and are offered effective contraception; termination is
recommended if pregnancy occurs.43 Progesterone-only
contraceptives—oral desogestrel, intramuscular
medroxyprogesterone, and etonogestrel implants—avoid the
prothrombotic effects of combined oral contraceptives. The
levonorgestrel releasing coil is effective, but poor tolerance of
potential vasovagal episodes mandates insertion in hospital.
Emergency hormonal contraception is safe after unprotected
intercourse. Non-obstetric surgical intervention also poses risks
and its indication requires careful evaluation.
Specific medical treatment (table 2 )
High dose calcium channel blockade
About 10% of patients with IPAH have a positive response to
vasoreactivity testing at right heart catheterisation. Observational
studies suggest that half of these patients exhibit long term
clinical responses to high dose calcium channel blockade (such
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BMJ 2013;346:f2028 doi: 10.1136/bmj.f2028 (Published 16 April 2013)
as diltiazem titrated to 480-720 mg/day or nifedipine titrated to
60-120 mg/day), with near normalisation of prognosis.46 47 No
evidence exists for this treatment in other forms of PAH, and
because of the potential negative inotropic effect, treatment
should not be started without a positive acute vasoreactive test.
Prostanoids
Prostacyclin is a vasodilator with antiproliferative effects.
Infused continuously through an indwelling central line, it was
the first PAH specific drug shown to be efficacious in a small
RCT, demonstrating improvements in exercise capacity,
haemodynamics, and, uniquely, survival.48 It has a half life of
about six minutes, is unstable at room temperature, and
intravenous administration has an associated risk of line
infection. Alternative routes of administration were therefore
developed. A larger RCT found that nebulised iloprost (half life
about 30 minutes) improved exercise capacity and
haemodynamics when given seven times a day.49 Because of its
superior stability, iloprost is also given intravenously in some
centres. Treprostinil (half life about four hours) was shown, in
a very large RCT, to significantly improve exercise capacity
when given by continuous subcutaneous infusion.50 Further
RCTs also showed significant improvements in exercise capacity
when it was given by nebulised and intravenous routes.51 52 Oral
prostanoids have also been assessed with large RCTs, but results
have generally been disappointing, and studies are ongoing.53-56
Endothelin receptor antagonists
Endothelin is a potent vasoconstrictor of vascular smooth
muscle. Two oral endothelin receptor antagonists are currently
licensed, bosentan and ambrisentan, on the basis of well
conducted RCTs showing improved exercise capacity and time
to clinical worsening.57 58 Bosentan causes reversible
abnormalities in liver function tests in 5-10% of patients, so
monthly monitoring is needed.59
Phophodiesterase-5 inhibitors
Nitric oxide acts via cyclic GMP to increase pulmonary vascular
relaxation and reduce cellular proliferation and is degraded by
phophodiesterase-5. Two oral phophodiesterase-5 inhibitors
(sildenafil and tadalafil) improved exercise and functional
capacity in large well conducted RCTs.60 61 These drugs have
important interactions with nitrates, so concomitant use is
contraindicated.
Treatment approach
Guidelines suggest starting oral treatment for patients with PAH
in WHO functional classes II and III, and considering parenteral
prostanoids in suitable patients in class IV or those with poor
prognostic markers in class III (box 2).43 If response to treatment
is suboptimal, switching or adding further drugs is suggested.43
Sequential addition of drugs to achieve predefined treatment
goals in six minute walk distance, maximal oxygen capacity,
and peak systolic blood pressure was associated with improved
outcome compared with patients whose treatment had been
escalated in a non-standardised manner.62 Several RCTs of
combination therapy are ongoing. Assessment of the patient’s
ability to use complex prostanoid therapy and adherence to
treatment require the support of experienced healthcare
professionals.
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CLINICAL REVIEW
Chronic thromboembolic pulmonary hypertension
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About two thirds of patients with CTEPH are candidates for
pulmonary endarterectomy. This operation offers the best
prospect of substantial improvement in symptoms,
haemodynamics, and long term survival, as shown by a recent
UK observational study.8 Surgical eligibility criteria are not
clearly established, and suitable candidates are identified after
assessment at specialist surgical centres (Papworth Hospital in
the UK). Perioperative mortality in large volume centres is now
less than 5%. In inoperable cases PAH specific drugs are often
used, although evidence is suboptimal. Do not delay referral for
surgery for trials of medical therapy, although such treatment
can be used to support patients with severe CTEPH as a “bridge”
to surgery.
Other non-medical treatments
Lung transplantation (usually double lung), which has overall
five year survival of around 50%, is indicated in severe PAH
or inoperable CTEPH if medical management fails.63 Atrial
septostomy decompresses the pressure loaded heart and may
be useful in patients with severe PAH who have intractable
syncope but not severe hypoxaemia, or as a bridge to
transplantation.64 Supervised exercise training improves exercise
capacity, but effects on haemodynamics and prognosis are
unclear.65
What challenges are on the horizon?
Despite progress in the management of PAH, it remains a life
shortening condition. Understanding disease mechanisms and
developing new treatments is a focus of international
collaboration. Recent data have shown efficacy for drugs
targeting existing pathways, such as macitentan (endothelin
receptor antagonist)66 and riociguat (nitric oxide pathway via
soluble guanylate cyclase stimulation).67 68 Selexipag,69 a
prostacyclin receptor agonist, is also under investigation. Despite
promising effects on pulmonary haemodynamics the tyrosine
kinase inhibitor, imatinib, has recently been withdrawn from
licensing application, partly because of safety concerns.70 Studies
with stem cell therapy are ongoing.71 The role of mechanical
treatments, such as cardiac resynchronisation and right
ventricular assist devices, in PAH are of interest.72 73 The optimal
treatment of PH-LHD and PH-Lung is unclear and drugs are
being studied in phase III trials. Pulmonary artery balloon
angioplasty is being investigated in patients with CTEPH who
are not amenable to pulmonary endarterectomy.74 Future
availability of generic oral drugs for pulmonary hypertension
may lead to inappropriate prescribing in PH-LHD and PH-Lung.
It may also increase late referral to specialist centres and delays
in escalation of treatment.
Improved diagnostics and treatments provide increasingly
complex choices for patients and healthcare professionals in
this rare illness. The delivery of care through specialist centres
is increasingly advocated worldwide as a cost effective way to
deliver high quality care.43 Education on disease trajectory,
provision of psychological support, and access to social and
end of life care are championed by patients and their
representative organisations, and they are key to improving the
quality of life for patients with pulmonary hypertension.75
We thank Heather Allen for her help with fig 1.
Contributors: DGK, CAE, IS, and RC conceived and designed the article
and approved the final manuscript. DGK is guarantor.
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Box 2 WHO functional classes
Class I: Patients with pulmonary hypertension but in whom ordinary physical activity does not cause undue symptoms
Class II: Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest but ordinary
physical activity causes undue dyspnoea or fatigue, chest pain, or near syncope
Class III: Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest but less
than ordinary activity causes undue dyspnoea or fatigue, chest pain, or near syncope
Class IV: Patients with pulmonary hypertension who cannot carry out any physical activity without symptoms. These patients manifest
signs of right heart failure. Dyspnoea or fatigue may be present at rest. Discomfort is increased by any physical activity

Tips for non-specialists

Consider pulmonary hypertension as a cause of progressive unexplained breathlessness
Echocardiography is the most useful non-invasive test for investigating pulmonary hypertension but estimates systolic, not mean,
pulmonary artery pressure
Computed tomography pulmonary angiography is useful for assessing suspected pulmonary hypertension and also allows estimation
of cardiac chamber size
A large left atrium suggests that pulmonary hypertension is more likely to be caused by left heart disease
Pulmonary hypertension should not be empirically treated until a clear diagnosis is established
If a patient has suspected severe pulmonary hypertension remember that the differential diagnosis is wide and outlook has improved
considerably over the past 10 years

Additional educational resources

Resources for healthcare professionals
European Society of Cardiology (www.escardio.org/guidelines)—Guidelines for the management of pulmonary hypertension
Pulmonary Hypertension Association UK (www.paheducation.co.uk)—elearning course for healthcare professionals developed to educate
non-specialist healthcare professionals including general practitioners, nurses, and clinicians about pulmonary hypertension and its
management
Pulmonary Hypertension Online University (www.phaonlineuniv.org)—Specialist internet resource for continuing medical education
Pulmonary Vascular Research Institute (www.pvri.info)—Independent medical research organisation devoted to increasing the awareness
and knowledge of pulmonary vascular diseases and to facilitating advances in the treatment of affected people worldwide

Resources for patients

UK Pulmonary Hypertension Patients Association (www.phassociation.uk.com)—Supports adults and children with pulmonary hypertension
and their families
PHA Europe (www.phaeurope.org)—Information for patients with pulmonary hypertension as well as their family and friends
UK Raynaud’s and Scleroderma Association (www.raynauds.org.uk)—Supports patients with Raynaud’s syndrome and scleroderma
The Sommerville Foundation (www.thesf.org.uk)—Supports young people and adults born with a heart condition (congenital)

Competing interests: All authors have completed the ICMJE uniform
disclosure form at www.icmje.org/coi_disclosure.pdf (available on
request from the corresponding author) and declare: no support from
any organisation for the submitted work; DGK has received speaker
fees, attended advisory boards, and received funding to attend meetings
from Actelion, Bayer, Pfizer, United Therapeutics, Lily, and GSK; CAE
has received speaker fees and attended advisory boards for Actelion,
Bayer, and GSK; IS has received travel funding from Actelion and GSK;
RC has received speaker fees from Actelion and GSK and has attended
advisory boards for Actelion, Bayer, and GSK. The department has
received funding for research and education through unrestricted grants
from Actelion, Bayer, and Pfizer.
Provenance and peer review: Commissioned; externally peer reviewed.
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BMJ 2013;346:f2028 doi: 10.1136/bmj.f2028 (Published 16 April 2013)
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Tables

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Table 1| Pulmonary hypertension in patients with normal left ventricular systolic function: features useful in discriminating between
idiopathic pulmonary arterial hypertension and pulmonary hypertension caused by left ventricular diastolic dysfunction

Factor Idiopathic pulmonary arterial hypertension Diastolic dysfunction

Age Younger Older9
Comorbidities None Essential hypertension, atrial fibrillation, diabetes76
Electrocardiography Right axis deviation, right ventricular hypertrophy, ST Left axis deviation, left ventricular hypertrophy, ST
depression inferiorly and anteriorly depression laterally
Echocardiography
Left atrial size Normal Large76
Mitral flow and tissue Doppler Normal E/E′ >15*77
Cardiac magnetic resonance imaging
Morphology Ventricular mass index† often raised Ventricular mass index† often normal37
Septal position Systolic eccentricity index‡ often raised Systolic eccentricity index‡ often normal37
Function Right ventricular function often moderately or severely Right ventricular function often normal or mildly impaired37
impaired
Right heart catheter: Pulmonary arterial wedge pressure normal Pulmonary arterial wedge pressure raised43

*Ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E′); †Ratio of right ventricular mass to left ventricular mass; ‡Ratio of
maximal short axis left ventricular diameters parallel and perpendicular to interventricular septum.

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Table 2| Licensed drugs for treating pulmonary hypertension

BMJ: first published as 10.1136/bmj.f2028 on 16 April 2013. Downloaded from http://www.bmj.com/ on 3 August 2020 at Hudson Valley VAMC. Protected by copyright.
Drug Randomised controlled trial Administration Important or common side effects Important complications
Prostanoid
Epoprostenol Barst and colleagues48 Intravenous Nausea, headache, leg pain, jaw pain, flushing, Line infection
diarrhoea
Iloprost AIR49 Nebuliser; intravenous As for eposprostenol but less severe when Line infection with intravenous
nebulised administration
Treprostinil Simonneau and colleagues50 Subcutaneous As for eposprostenol; infusion site pain for
subcutaneous administration
TRIUMPH51 Nebuliser; intravenous
TRUST52
Endothelin receptor antagonists
Bosentan BREATHE-157 Oral Abnormal liver function tests in 10% of
patients; teratogenecity
Ambrisentan ARIES-1 and 258 Oral Peripheral oedema
Phosphodiesterase-5 inhibitors
Sildenafil SUPER-160 Oral Headache, indigestion, nasal stuffiness, blurred Non-arteritic ischaemic optic
vision, visual colour change neuropathy
Tadalafil PHIRST61

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Figures

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Fig 1 Classification of adult pulmonary hypertension. The condition can be caused by narrowing of the pulmonary arterial
tree as a result of vasculopathy (group 1) or webs and stenoses of chronic thromboembolic disease (group 4). Optimal
treatments are generally defined for groups 1 and 4. More commonly, it is associated with left heart disease (group 2) or
lung disease (group 3), and optimal treatments are unclear. Several conditions associated with pulmonary hypertension
have multifactorial or unclear mechanisms (group 5). *Chronic haemolytic anaemia will probably be in group 5 in next
classification update

Fig 2 Diagnostic pathway for patients with suspected pulmonary hypertension

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Fig 3 Echocardiographic assessment of pulmonary hypertension. RA=right atrium; RV=right ventricle; LA=left atrium; LV=left
ventricle

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Fig 4 Overview of patient pathway at a specialist centre

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Fig 5 Computed tomography assessment of pulmonary hypertension. RA=right atrium; RV=right ventricle, LA=left atrium;
LV=left ventricle; IVS, interventricular septum; PA, pulmonary artery; Ao, aorta; CTEPH=chronic thromboembolic pulmonary
hypertension

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